Angiotensin II negatively modulates cytokine-induced nitric oxide production by blocking iNOS expression via the AT1 receptor in vascular smooth muscle cells.
Does Angiotensin II inhibit cytokine-stimulated inducible nitric oxide synthase expression in cultured vascular smooth muscle cells?
Angiotensin II negatively modulates cytokine-induced NO production by blocking iNOS expression via the AT1 receptor in vascular smooth muscle cells, potentially involving protein kinase C.
In cultured vascular smooth muscle cells (VSMC), inflammatory cytokines such as interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha stimulated nitric oxide (NO) production via the expression of an inducible type of NO synthase (iNOS). A potent vasoconstrictor, angiotensin II (Ang II), which causes a rapid phospholipase C-mediated phosphoinositide hydrolysis via the Ang II type 1 (AT1) receptor in VSMC, by itself did not stimulate the production of nitrite, a stable metabolite of NO, but dose dependently inhibited the IL-1 beta-induced nitrite production. This inhibitory effect of Ang II was blocked by an AT1 receptor antagonist, CV-11974, but not by an Ang II type 2 receptor antagonist, PD 123319. The presence of Ang II during the early induction phase of iNOS was required for this inhibition. Consistently, Ang II suppressed IL-1 beta-induced increases in iNOS mRNA and protein levels. Ang II also inhibited increases in nitrite production and iNOS mRNA and protein levels caused by tumor necrosis factor alpha. A protein kinase C-activating phorbol ester, phorbol 12-myristate 13-acetate, and a membrane-permeable diacylglycerol, 1,2-dioctanoyl-glycerol, similarly inhibited the IL-1 beta-induced nitrite production and iNOS mRNA and protein expression, although repetitive additions were needed in the case of diacylglycerol. These results indicate that Ang II negatively modulates cytokine-induced NO production by blocking iNOS expression via the AT1 receptor in VSMC and suggest that protein kinase C could be involved in this process.
Nakayama et al. (Fri,) conducted a other in In vitro study (vascular smooth muscle cells). Angiotensin II vs. IL-1 beta or TNF-alpha alone was evaluated on Nitrite production and iNOS mRNA and protein levels. Angiotensin II negatively modulates cytokine-induced nitric oxide production by blocking iNOS expression via the AT1 receptor in vascular smooth muscle cells.